SUPPLEMENTAL IRON EXACERBATES AMINOGLYCOSIDE OTOTOXICITY IN-VIVO

There is increasing evidence to suggest that free :radical generation is central to a variety of pathological processes, including drug toxi city. Studies demonstrating the ability of gentamicin to facilitate th e generation of radical species suggest that this process plays an imp ortant role in aminoglycoside-induced ototoxicity. Because:transition metals, particularly iron, play an important role in the production of free radicals and the generation of reactive oxygen species, we sough t to determine whether gentamicin-induced ototoxicity is exacerbated b y increases in serum iron levels. To this end, we assessed the effects of supplemental iron administration (2 mg/kg/day and 6 mg/kg/day) on changes in auditory function induced by co-administration of gentamici n (100 mg/kg/day for 30 days). Experiments were carried out on pigment ed guinea pigs initially weighing 250-300 g. Changes in cochlear funct ion were characterized as shifts in compound action potential (CAP) th resholds, estimated every third day throughout the treatment period by use of chronic indwelling electrodes implanted at the round window, v ertex, and contralateral mastoid. Results showed that animals receivin g iron in combination with gentamicin demonstrated a more rapid and pr ofound elevation ill CAP thresholds compared with animals receiving ge ntamicin alone. This effect occurred in a dose-dependant manner. Anima ls receiving supplemental iron alone maintained normal CAP thresholds throughout the treatment period. There was no statistically significan t difference in serum gentamicin levels between groups receiving genta micin alone or gentamicin plus iron. These results provide further evi dence of the recently reported intrinsic role of iron in aminoglycosid e ototoxicity, and highlight a potential risk of aminoglycoside admini stration in patients with elevated serum iron. (C) 1998 Elsevier Scien ce B.V.